Simple linear amines such as ethylenediamine and diethylenetriamine have long been known as excellent coordinating ligands towards a range of transition and other heavy metal ions. The resulting metal complexes, being metal chelates, are usually significantly thermodynamically more stable than corresponding unidentate amine complexes of, for example, ammonia or methylamine.
In the past, various ligands including linear amines, have been attached to organic polymers supports. However, these are often difficult to synthesise in a manner that maintains the ion co-ordination properties of the ligand because of the inherent lipophilicity of the organic backbone. Organic polymer substrates are generally expensive which tends to make organic-polymer-bound ligands relatively expensive.
Amines have also been attached to inorganic supports. A range of simple amines, including ammonia, ethylenediamine, diethylenetriamine, triethylenetetramine and tetraethylenepentamine have been immobilised by chemically binding them via spacer groups to silicate surfaces to produce insoluble particles that will form complexes with and retain selected cations.
Techniques for binding these simple amines to inorganic supports such as silicon dioxide or silica gel (and other silicon containing substances, including glass), to aluminas and to other insoluble elemental oxides have been described. For example, the amine may be reacted with a spacer group such as (3-chloropropyl)-trimethoxysilane, (3-chloropropyl)-triethoxysilane or a range of other related functionalised alkylsilanes, such that the product is capable of attachment to silicon dioxide via one or more covalent bonds. This is one of several methods for immobilising simple ligands on a solid support. The above reaction sequence may be changed so that the spacer group is first attached to the solid support followed by immobilisation of the amine ligand by reaction with the free terminal group of the spacer. Specifically, the immobilisation of tetraethylenepentamine by this technique is known from Czech Patent No. 177,563 to Vynalezu. Further examples of this type are disclosed in U.S. patents of Bradshaw et al (U.S. Pat. No. 4,952,321), Hancock and Howell (U.S. Pat. No. 4,203,952) and Plueddemann (U.S. Pat. No. 4,071,546). These workers claim the attachment of a number of linear chain derivatives to solid substrates such as silica gel at one end of the linear chain using between one and three bonds to the silica.
Linear polyethyleneimines may be represented by the formula H.sub.2 N(CH.sub.2 CH.sub.2)NH!.sub.n H (where n is typically about 7 to 2000). This linear chain material is expected to also bind certain metal ions strongly. A chromatographic column packing for the purification and separation of anions and more specifically, anionic protein species has been described in Ramsden, U.S. Pat. No. 4,450,486. This patent discloses the preparation of a product that consists of linear non-crosslinked polyethyleneimine bound by a silane reagent to silica gel. The product, however, is limited to the use of silica gel having an average particle diameter of about three to seventy microns.
A related disclosure is found in European Patent No. 403,700 to Crane and Kakodkar, in which linear non-crosslinked polyethyleneimine of molecular weight 400 to 1800, is covalently bound to a silica-based solid-phase support. This product serves as an affinity chromatography matrix. The preparation of surface modified silica materials for use as ion-exchangers is disclosed in Jansen et al., "Absorption of Proteins on Porous and Non-Porous Poly(ethyleneimine) and tentacle-Type Anion Exchangers (Journal of Chromatography, vol. 522, 1990, 77-93).
A known application of immobilised simple linear amines is the retention by complexation of ions, such as the generally toxic ions of bismuth, cobalt, chromium, copper, gold, iron, lead, mercury, nickel, radium, silver, tin and zinc, at small concentrations of these ions, even in parts per billion, while not appreciably complexing the low toxicity ions of sodium, potassium, calcium and magnesium at concentrations even thousand of times greater. Because the immobilised-ligand capacity is not consumed by the low toxicity ions, the loading-cycle time will be longer (or less material will be needed) than if both the "unwanted" and the "low toxicity" ions were removed together.
For applications of the above type it is desirable to bind the amine ligand to larger particles of silica gel than, for example, taught in the Ramsden patent.
Larger particles enable the immobilised material to be employed in applications requiring a lower pressure drop access and packed column than can be achieved with smaller particles.
The use of coarse solid support particles, larger than those mentioned in the Ramsden patent, is expected to produce less satisfactory results when bound to large amines such as polyalkyleneimines. Such coarse support particles will have lower effective surface area, per unit weight of support, for attachment of the polyalkyleneimine. In some cases, especially when the molecular weight of the polyalkyleneimine is about 50,000, the product is a gummy mass that has even lower complexation capacity, due to the adherence between particles. Some or all of these problems may account for the general belief in the art that large amines must be bound to relatively small support particles.
A further difficulty with using inorganic materials having hydroxyl groups as the support is that they are highly susceptible to degradation in alkaline conditions. Silica gel is particularly susceptible to degradation. It is known that immobilised linear polyalkyleneimines are not completely stable and over time will lose their ion complexing ability. While not wishing to be bound by theory, it appears that the silica gel support can still be attacked by hydroxides even when coated with the linear polyalkleneimines.
European Patent No. 403700 refers to the stability of silica gel as a support for affinity chromatography. This patent teaches the immobilisation of enzymes on a support comprising linear non-crosslinked polyethyleneimine of molecular weight 400-1800 covalently bound to silica particles of 200 microns or less. However, the stability required for an enzyme support is quite different to that required for a support which complexes heavy metals: Further, as discussed above, this small particle size is not suitable for many applications. For example, conditions used for binding heavy metals would normally destroy or denature enzymes.
Branched polyamines also bind strongly to a range of transition and other heavy metal ions. Studies on free (non-immobilised) branched polyethyleneimines show that the effective volume of the polymer varies according to pH. The polymer is large when the nitrogens are protonated due to repulsion, and contracts due to hydrogen bonding when the nitrogens are deprotonated.
The branching present in branched polyalkyleneimine can occur at its nitrogen moieties (as shown by the example of polyethyleneimine, see FIG. 1). The ratio of primary to secondary to tertiary amines present will depend upon the degree of branching and can, for example, be 1:2:1. In this case, the primary and tertiary amines would comprise half of the nitrogen groups in each molecule.
However, as mentioned above, it has hitherto not been thought to be possible to bind branched amines to a solid support having a large particle size so as to produce a product having a useful complexation capacity.
U.S. Pat. No. 5,190,660 to Lindoy and Eaglen discloses a technique for binding linear polyethyleneimine to silica gel. This patent aims to overcome the problems associated with the Ramsden patent in which the product was limited to silica of small particle sizes. U.S. Pat. No. 5,190,660 describes a method by which linear polyethyleneimine may be immobilised onto silica having particle sizes larger than that of the Ramsden patent. U.S. Pat. No. 5,190,660 makes a general statement that commercially available polyethyleneimines may contain a small amount of branched and cross-linked material as opposed to linear material. No attempt is made in the patent to isolate or define the properties of immobilised branched polyethyleneimine silica gel compositions and any non-linear product is treated more as a by-product or an impurity. The patent teaches away from any useful product which may be obtained from branched polyethyleneimines. The patent further does not make any reference to the stability of the product. As this patent is directed towards liner polyethyleneimines, the products described therein would presumably also have the above mentioned problems associated with lack of stability.
It would be desirable to be able to effectively link branched polyalkyleneimines with larger solid support particles, especially those having a size range from about 200 mesh to about 20 mesh, which corresponds to a diameter range of about 74 microns to about 850 microns. Such larger particles would enable bound branched polyalkyleneimines to be employed in applications requiring less pressure drop than is created with smaller particles. Thus, for example, large volume applications would be possible. Generally, large volume applications are benefited by maintaining a low pressure drop across the treatment bed.
It would also be desirable to obtain a product which is relatively stable under a wide range of operating conditions. Especially desirable is a product which may be regenerated without substantial efficiency loss.
After much trial and experimentation, new immobilised branched polyalkyleneimines have now been prepared, isolated and various useful applications have been found.